One outbred (CF1) and four inbred (BALB/c, C57, CBA and C3H) strains of mice were tested for susceptibility to Babesia microti of human origin. Of these, intact C3H mice developed higher parasitemia than all other intact mice, while BALB/c mice developed the highest parasitemia among splenectomized mice. Susceptibility was not related to H-2 haplotype in any obvious way. Because C3H and BALB/c mice developed relatively high initial peak parasitemias, the parasite was serially passaged in both of these mouse strains in an attempt to increase parasite virulence. After 30 passages in BALB/c and 49 passages in C3H mice over a period of 12 months, maximum parasitemias were 50 times higher than those observed initially. After the peak parasitemias of these two mouse-adapted parasites had stabilized, the relationship between onset and level of maximum parasitemia and number of parasites inoculated was determined. With both C3H- and BALB/c-adapted parasites, as inoculum size increased, the time required to reach maximum parasitemia decreased and the level of maximum parasitemia increased. Studies involving infection of either mouse strain with parasites adapted to the heterologous mouse strain indicated that C3H mice were more susceptible than BALB/c mice to homologous or heterologous parasites. These data suggest that the virulence of B. microti to the mouse can be increased by prolonged passage in this host. Once adaptation to this host species has occurred, virulence appears to be more dependent on the innate susceptibility of the mouse strain than on adaptation of the parasites to a particular strain of mouse.

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It is shown that liposomes containing (i) a fluorescein-labeled murine histocompatibility antigen and the G protein of vesicular stomatitis virus or (ii) H-2Kk and fluorescein-labeled viral protein (FITC-G) can elicit H-2-restricted syngeneic antiviral cytotoxic T 'cells as assayed by 5tCr release from appropriate virus-infected target cells. Fluorescence recovery after photobleaching was -used to measure the diffusion coefficients of these reconstituted proteins in four different sam-ples: (i) FITC-H-2Kk; jiU) FITC-H-2Kk and G; (iii) FITC-G; and (iv) FITC-G and H-2K . The same rate of lateral diffusion (D' = 1 X 10-8 cm2/sec at 37C in 25% cholesterol/75% dimyristoylphosphatidylcholine) was obtained in every case. Both proteins, fluorescent as well as nonfluorescent, could be patched by using specific antibodies. When G was patched with antibody, FITC-H2Kk did not copatch. When H-2Kk was patched with antibody, FITC-G did not copatch. These diffusion and patching measurements rule out the possibility that these proteins have either extensive oligomeric associations or strong specific pairwise associations.There is now much evidence that virus-specific cytotoxic T lymphocytes (CTL) are dually specific for.virus and for selfcell surface antigens encoded by the major histocompatibility complex (1). Effector lymphocytes sensitized against virus-infected cells of a given haplotype will lyse virus-infected cells of the same haplotype with much higher efficiency than virus-infected cells of a different haplotype. A similar restriction holds for the afferent immune response. Virus-specific H-2-restricted secondary elicitation of CTL has been demonstrated by using membrane fragments as well as reconstituted membranes (2-11). These studies show that both viral protein and H-2 antigen must be present in the same reconstituted membrane in order to elicit the cellular response.Three models can be considered, based on alternative hypothetical structures for the T-cell receptor(s). In one model, a specific molecular complex between viral protein and transplantation antigen preexists in the target membrane before interaction with the T cell and is recognized by the T-cell receptor. In the second model, a close physical association of the two antigens is stabilized only during their interaction with the Tcell receptor. In the third model, no close physical or chemical association between viral protein and transplantation antigen exists prior to, or during, interaction with the T cell. (This is the two-receptor or "dual receptor" model.) The T-cell receptor(s) involved in the secondary elicitation of CTL is presumed to be on precytotoxic T cells or on T helper cells or on both.One biophysical approach to this problem is to use fluorescently labeled membrane components so that the distribution, motion, and interaction of these components can be studied by using optical techniques. In the work described here, purified G protein (G) of vesicular stomatitis virus (VSV) and purified H-2Kk protein were fluorescently labeled an...

Vesicular stomatitis virus (VSV) infection of beige (bg/bg) mice induced levels of natural killer cytolytic activity comparable to that of uninfected normal bg/+ controls, but considerably less than natural killer activity in VSV-infected bg/+ mice. In contrast, VSV-infected bg/bg and bg/+ mice had essentially equivalent amounts of anti-VSV cytotoxic T-lymphocyte and antibody activity. VSV infection induced comparable levels of interferon in both bg/bg and bg/+ mice. Therefore, the decreased natural killer activity in bg/bg mice could not be attributed to an inability to produce interferon.